A longitudinal prospective study of adolescents at high risk for affective disorder is continuing. A biological marker, the suppression of plasma melatonin by light, differentiates the "high- risk" adolescents from a control adolescent group. CSF dynorphin A1-8 immunoreactivity is significantly elevated in Tourette's Syndrome compared to age and sex matched controls. The degree of elevation is significantly correlated with severity of obsessive-compulsive behavior (but not with severity of motor tics), suggesting that this peptide may play a role in pathophysiology of this disorder. Post-mortem ventricular fluid (PMVF) was obtained at autopsy from subjects with Alzheimer's disease (AD), Huntington's disease (PD) and controls dying of cause not related to the CNS. Measurements of galanin, neuropeptide Y, and somatostatin revealed that all were significantly elevated in every patient group compared to the controls, findings that are contrary to in vivo lumbar CSF studies, suggesting that PMVF may not be a valid approach to the study of neuropeptides in diseases states.